Antimicrobial resistance (AMR) is a growing global health threat driven largely by irrational antibiotic prescribing practices. Despite the development of stewardship frameworks, inappropriate antibiotic use persists across primary care, hospitals, dental practice, veterinary care, and community settings. This narrative review synthesizes global evidence on barriers to rational antibiotic prescribing and identifies opportunities for improvement, with particular emphasis on low- and middle-income countries (LMICs). Literature indicates that prescribing behavior is influenced by multilevel determinants including clinician knowledge, patient expectations, diagnostic uncertainty, health system limitations, pharmaceutical pressures, sociocultural norms, and policy enforcement gaps. Evidence shows that patient demand, time constraints, lack of diagnostic tools, and inadequate stewardship support contribute significantly to inappropriate antibiotic use. In LMICs, structural challenges such as drug accessibility without prescriptions, weak regulation, and limited training exacerbate irrational use. Behavioral drivers and cultural prescribing norms further influence decision-making. This review proposes a conceptual framework integrating individual, interpersonal, organizational, and policy-level determinants influencing prescribing behavior. Strengthening stewardship programs, improving diagnostic capacity, enhancing training, regulating antibiotic access, and addressing patient expectations are critical strategies for rational antibiotic use. A systems-based approach is essential to mitigate AMR and ensure sustainable antibiotic effectiveness.

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